Clinical pharmacology and toxicology of cocaine

Cocaine abuse has produced a major epidemic health problem in North America in the 1980s. The abuse of cocaine is maintained by the drug's effects on brain reward systems, mediated at least in part by its dopaminergic action. The patterns and consequences of use are best understood by considering the pharmacokinetics (rapid absorption and delivery to the brain, relatively short half-life) and the pharmacodynamics (intense central and peripheral neural stimulation). Cocaine is used therapeutically as a topical and local anaesthetic. Toxicity occurs primarily in cocaine abusers, but also occasionally after therapeutic dosing. Medical complications reflect primarily excessive central nervous system stimulation and excessive vasoconstriction, the latter resulting in severe hypertension and/or organ ischaemia with associated organ injury. Most deaths that result from medical complications of cocaine intoxication are sudden and occur before medical intervention is possible. Other complications of cocaine abuse with severe personal and social consequences include traumatic deaths and injuries, and reproductive disturbances, as well as transmission of infectious diseases, especially AIDS. Cocaine addiction is clearly a problem, although the number of addicts is unknown. Pharmacologic treatment of cocaine addiction has as yet been unsuccessful. Psychosocial approaches remain the mainstay of therapy.